ES2327873T3 - Compuestos de piperazina sustituidos y su utilizacion como inhibidores de la oxidacion de acidos grasos. - Google Patents
Compuestos de piperazina sustituidos y su utilizacion como inhibidores de la oxidacion de acidos grasos. Download PDFInfo
- Publication number
- ES2327873T3 ES2327873T3 ES07008429T ES07008429T ES2327873T3 ES 2327873 T3 ES2327873 T3 ES 2327873T3 ES 07008429 T ES07008429 T ES 07008429T ES 07008429 T ES07008429 T ES 07008429T ES 2327873 T3 ES2327873 T3 ES 2327873T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- formula
- hydroxy
- hydrogen
- substituted
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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- 230000003647 oxidation Effects 0.000 title description 24
- 238000007254 oxidation reaction Methods 0.000 title description 24
- 235000014113 dietary fatty acids Nutrition 0.000 title description 10
- 239000000194 fatty acid Substances 0.000 title description 10
- 229930195729 fatty acid Natural products 0.000 title description 10
- 150000004665 fatty acids Chemical class 0.000 title description 10
- 239000003112 inhibitor Substances 0.000 title description 7
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical class C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 161
- 201000010099 disease Diseases 0.000 claims abstract description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 15
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 7
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 7
- 206010022562 Intermittent claudication Diseases 0.000 claims abstract description 6
- 208000010125 myocardial infarction Diseases 0.000 claims abstract description 6
- 206010003130 Arrhythmia supraventricular Diseases 0.000 claims abstract description 5
- 208000007718 Stable Angina Diseases 0.000 claims abstract description 5
- 206010047281 Ventricular arrhythmia Diseases 0.000 claims abstract description 5
- 206010002388 Angina unstable Diseases 0.000 claims abstract description 4
- 208000007814 Unstable Angina Diseases 0.000 claims abstract description 4
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims abstract description 4
- -1 2-methylbenzothiazol-5-yl Chemical group 0.000 claims description 92
- 125000000217 alkyl group Chemical group 0.000 claims description 76
- 125000001424 substituent group Chemical group 0.000 claims description 53
- 238000002360 preparation method Methods 0.000 claims description 51
- 125000003118 aryl group Chemical group 0.000 claims description 50
- 239000001257 hydrogen Substances 0.000 claims description 42
- 229910052739 hydrogen Inorganic materials 0.000 claims description 42
- 229910052736 halogen Inorganic materials 0.000 claims description 37
- 150000002367 halogens Chemical class 0.000 claims description 37
- 125000003545 alkoxy group Chemical group 0.000 claims description 34
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 25
- 239000001301 oxygen Substances 0.000 claims description 25
- 229910052760 oxygen Inorganic materials 0.000 claims description 25
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
- 150000002431 hydrogen Chemical class 0.000 claims description 21
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 125000004193 piperazinyl group Chemical group 0.000 claims description 11
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
- 229910052717 sulfur Chemical group 0.000 claims description 8
- 239000011593 sulfur Chemical group 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
- 208000014674 injury Diseases 0.000 claims description 5
- 201000001068 Prinzmetal angina Diseases 0.000 claims description 3
- 208000009325 Variant Angina Pectoris Diseases 0.000 claims description 3
- 230000035939 shock Effects 0.000 claims description 3
- 230000008733 trauma Effects 0.000 claims description 3
- 125000006651 (C3-C20) cycloalkyl group Chemical group 0.000 claims description 2
- 208000029549 Muscle injury Diseases 0.000 claims description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 208000019622 heart disease Diseases 0.000 claims description 2
- 210000002027 skeletal muscle Anatomy 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 6
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 2
- 206010002383 Angina Pectoris Diseases 0.000 abstract description 7
- 230000001746 atrial effect Effects 0.000 abstract description 4
- 206010007559 Cardiac failure congestive Diseases 0.000 abstract description 3
- 208000021156 intermittent vascular claudication Diseases 0.000 abstract description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 81
- 125000001072 heteroaryl group Chemical group 0.000 description 41
- 238000006243 chemical reaction Methods 0.000 description 38
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 239000000243 solution Substances 0.000 description 29
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- 238000000034 method Methods 0.000 description 27
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 25
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 25
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 25
- 125000000623 heterocyclic group Chemical group 0.000 description 24
- 239000002904 solvent Substances 0.000 description 24
- 125000004093 cyano group Chemical group *C#N 0.000 description 23
- 239000008103 glucose Substances 0.000 description 23
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 125000000753 cycloalkyl group Chemical group 0.000 description 21
- 125000003342 alkenyl group Chemical group 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- 230000002829 reductive effect Effects 0.000 description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 150000001412 amines Chemical class 0.000 description 18
- 239000003826 tablet Substances 0.000 description 18
- 239000004480 active ingredient Substances 0.000 description 17
- 125000000304 alkynyl group Chemical group 0.000 description 17
- 125000000392 cycloalkenyl group Chemical group 0.000 description 17
- 125000004432 carbon atom Chemical group C* 0.000 description 15
- 230000010412 perfusion Effects 0.000 description 15
- 239000002253 acid Substances 0.000 description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 13
- 239000000843 powder Substances 0.000 description 13
- 150000003839 salts Chemical class 0.000 description 13
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 12
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- 125000002947 alkylene group Chemical group 0.000 description 11
- 210000002216 heart Anatomy 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 125000004414 alkyl thio group Chemical group 0.000 description 10
- 125000004104 aryloxy group Chemical group 0.000 description 10
- 125000004429 atom Chemical group 0.000 description 10
- 239000011347 resin Substances 0.000 description 10
- 229920005989 resin Polymers 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 229930194542 Keto Natural products 0.000 description 9
- 125000002252 acyl group Chemical group 0.000 description 9
- 125000004442 acylamino group Chemical group 0.000 description 9
- 125000004423 acyloxy group Chemical group 0.000 description 9
- 125000005110 aryl thio group Chemical group 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 238000007796 conventional method Methods 0.000 description 9
- 230000034659 glycolysis Effects 0.000 description 9
- 125000005553 heteroaryloxy group Chemical group 0.000 description 9
- 239000004615 ingredient Substances 0.000 description 9
- 125000000468 ketone group Chemical group 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 9
- 150000003573 thiols Chemical class 0.000 description 9
- 125000000033 alkoxyamino group Chemical group 0.000 description 8
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 8
- 125000006598 aminocarbonylamino group Chemical group 0.000 description 8
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 8
- 230000000747 cardiac effect Effects 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
- 125000005368 heteroarylthio group Chemical group 0.000 description 8
- 125000004470 heterocyclooxy group Chemical group 0.000 description 8
- 125000004468 heterocyclylthio group Chemical group 0.000 description 8
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 8
- 239000012442 inert solvent Substances 0.000 description 8
- 238000005259 measurement Methods 0.000 description 8
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
- 125000000547 substituted alkyl group Chemical group 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 150000007530 organic bases Chemical class 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- IPCSVZSSVZVIGE-BFDQMJDGSA-N 5-tritiohexadecanoic acid Chemical compound C(CCCC(CCCCCCCCCCC)[3H])(=O)O IPCSVZSSVZVIGE-BFDQMJDGSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 5
- 150000002430 hydrocarbons Chemical group 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 239000006187 pill Substances 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 4
- BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 4
- TUADYTFWZPZZTP-UHFFFAOYSA-N 2-amino-4-methoxyphenol Chemical compound COC1=CC=C(O)C(N)=C1 TUADYTFWZPZZTP-UHFFFAOYSA-N 0.000 description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- XKLMZUWKNUAPSZ-UHFFFAOYSA-N N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl}acetamide Chemical compound COC1=CC=CC=C1OCC(O)CN1CCN(CC(=O)NC=2C(=CC=CC=2C)C)CC1 XKLMZUWKNUAPSZ-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 125000004181 carboxyalkyl group Chemical group 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 150000007529 inorganic bases Chemical class 0.000 description 4
- 230000002107 myocardial effect Effects 0.000 description 4
- 210000004165 myocardium Anatomy 0.000 description 4
- 230000036316 preload Effects 0.000 description 4
- 229930195734 saturated hydrocarbon Natural products 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 125000005017 substituted alkenyl group Chemical group 0.000 description 4
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 4
- RSRULPXKVAYTHK-UHFFFAOYSA-N 2-(2,4-dichlorophenyl)-1,3-benzoxazol-5-ol Chemical compound N=1C2=CC(O)=CC=C2OC=1C1=CC=C(Cl)C=C1Cl RSRULPXKVAYTHK-UHFFFAOYSA-N 0.000 description 3
- KGTDVVHOIPNXRY-UHFFFAOYSA-N 2-(2,4-dichlorophenyl)-5-methoxy-1,3-benzoxazole Chemical compound N=1C2=CC(OC)=CC=C2OC=1C1=CC=C(Cl)C=C1Cl KGTDVVHOIPNXRY-UHFFFAOYSA-N 0.000 description 3
- JLBPUGDFLNTMBC-UHFFFAOYSA-N 2-(4-fluorophenyl)-5-methoxy-1,3-benzoxazole Chemical compound N=1C2=CC(OC)=CC=C2OC=1C1=CC=C(F)C=C1 JLBPUGDFLNTMBC-UHFFFAOYSA-N 0.000 description 3
- IHBVNSPHKMCPST-UHFFFAOYSA-N 3-bromopropanoyl chloride Chemical compound ClC(=O)CCBr IHBVNSPHKMCPST-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 125000003710 aryl alkyl group Chemical group 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 235000015165 citric acid Nutrition 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 210000005246 left atrium Anatomy 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- FIBIQXIWYQVGAY-UHFFFAOYSA-N n-(2,6-dimethylphenyl)-3-piperazin-1-ylpropanamide Chemical compound CC1=CC=CC(C)=C1NC(=O)CCN1CCNCC1 FIBIQXIWYQVGAY-UHFFFAOYSA-N 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 238000006213 oxygenation reaction Methods 0.000 description 3
- 150000004885 piperazines Chemical class 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000001103 potassium chloride Substances 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 229960000213 ranolazine Drugs 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- JOMNTHCQHJPVAZ-YFKPBYRVSA-N (2s)-2-methylpiperazine Chemical compound C[C@H]1CNCCN1 JOMNTHCQHJPVAZ-YFKPBYRVSA-N 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 2
- UFFBMTHBGFGIHF-UHFFFAOYSA-N 2,6-dimethylaniline Chemical compound CC1=CC=CC(C)=C1N UFFBMTHBGFGIHF-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/56—Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D263/57—Aryl or substituted aryl radicals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/08—Radicals containing only hydrogen and carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/64—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Vascular Medicine (AREA)
- Neurology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Lubricants (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US43150602P | 2002-12-05 | 2002-12-05 | |
| US431506P | 2002-12-05 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2327873T3 true ES2327873T3 (es) | 2009-11-04 |
Family
ID=32507739
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES07008429T Expired - Lifetime ES2327873T3 (es) | 2002-12-05 | 2003-12-05 | Compuestos de piperazina sustituidos y su utilizacion como inhibidores de la oxidacion de acidos grasos. |
| ES03812835T Expired - Lifetime ES2287574T3 (es) | 2002-12-05 | 2003-12-05 | Compuestos de piperacina sustituidos y su utilizacion como inhibidores de la oxidacion de acidos grasos. |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES03812835T Expired - Lifetime ES2287574T3 (es) | 2002-12-05 | 2003-12-05 | Compuestos de piperacina sustituidos y su utilizacion como inhibidores de la oxidacion de acidos grasos. |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US7125876B2 (de) |
| EP (1) | EP1567525B1 (de) |
| JP (1) | JP2006510670A (de) |
| KR (1) | KR20050084182A (de) |
| AT (1) | ATE365737T1 (de) |
| AU (1) | AU2003300827B2 (de) |
| CA (1) | CA2508608A1 (de) |
| DE (2) | DE60328545D1 (de) |
| ES (2) | ES2327873T3 (de) |
| NZ (1) | NZ540548A (de) |
| WO (1) | WO2004052887A2 (de) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ541069A (en) * | 2003-01-03 | 2008-09-26 | Cv Therapeutics Inc | Piperazine derivatives as fatty acid oxidation inhibitors |
| US7271169B2 (en) * | 2004-09-08 | 2007-09-18 | Cv Therapeutics, Inc. | Substituted heterocyclic compounds |
| WO2007079003A2 (en) * | 2005-12-29 | 2007-07-12 | Bayer Schering Pharma Aktiengesellschaft | Amide inhibitors of leukotriene a4 hydrolase |
| KR101476379B1 (ko) * | 2011-11-30 | 2014-12-29 | 한국과학기술연구원 | 페녹시프로판올 유도체 및 이를 함유하는 약학적 조성물 |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2267104A1 (en) * | 1974-04-12 | 1975-11-07 | Ferlux Labo Sa | Hypotensive and antiarrhythmic piperazines - 1-(3-phenoxy-2-hydroxy propyl)-4-substd. piperazines |
| US4766125A (en) | 1981-06-23 | 1988-08-23 | Janssen Pharmaceutica N.V. | N-aryl-piperazinealkanamides useful for protecting hearts from myocardial injury caused by ischaemia, anoxia or hypoxia |
| US4567264A (en) | 1983-05-18 | 1986-01-28 | Syntex (U.S.A.) Inc. | Cardioselective aryloxy- and arylthio- hydroxypropylene-piperazinyl acetanilides which affect calcium entry |
| US4558129A (en) | 1983-05-18 | 1985-12-10 | Syntex (U.S.A.) Inc. | Benzodioxanyl-hydroxyethylene-piperazinyl acetanilides which effect calcium entry and β-blockade |
| US4588129A (en) * | 1983-09-06 | 1986-05-13 | Hudson Oxygen Therapy Sales Company | Nebulizer |
| US4788306A (en) * | 1987-04-03 | 1988-11-29 | American Home Products Corporation | Fluorooxirane carboxylates as hypoglycemic agents |
| JPH0730456Y2 (ja) | 1989-05-11 | 1995-07-12 | 株式会社神戸製鋼所 | ホイールクレーンのステアリング制御装置 |
| ES2177601T3 (es) | 1989-06-23 | 2002-12-16 | Syntex Llc | Ranolazina y pepeerazinas relacionadas para uso en el tratamiento de estados de choque. . |
| JPH03141258A (ja) | 1989-10-25 | 1991-06-17 | Kowa Co | 新規なピペラジン誘導体 |
| US5455045A (en) | 1993-05-13 | 1995-10-03 | Syntex (U.S.A.) Inc. | High dose formulations |
| HUP0002294A3 (en) * | 1997-05-26 | 2001-10-29 | Kowa Co | Cyclic diamine compounds and medicines containing the same |
| NZ520780A (en) * | 2000-02-18 | 2006-04-28 | Cv Therapeutics Inc | Partial fatty acid oxidation inhibitors in the treatment of congestive heart failure |
| WO2001062711A2 (en) * | 2000-02-22 | 2001-08-30 | Cv Therapeutics, Inc. | Substituted alkylene diamine compounds |
| US6677336B2 (en) | 2000-02-22 | 2004-01-13 | Cv Therapeutics, Inc. | Substituted piperazine compounds |
| AU2001238590A1 (en) | 2000-02-22 | 2001-09-03 | Cv Therapeutics, Inc. | Substituted piperazine compounds |
| NZ520782A (en) * | 2000-02-22 | 2004-03-26 | Cv Therapeutics Inc | Substituted piperazine compounds that are partial fatty acid oxidation inhibitors |
| US6451798B2 (en) | 2000-02-22 | 2002-09-17 | Cv Therapeutics, Inc. | Substituted alkyl piperazine derivatives |
| US6552023B2 (en) | 2000-02-22 | 2003-04-22 | Cv Therapeutics, Inc. | Aralkyl substituted piperazine compounds |
| US6693099B2 (en) * | 2000-10-17 | 2004-02-17 | The Procter & Gamble Company | Substituted piperazine compounds optionally containing a quinolyl moiety for treating multidrug resistance |
| SE0003795D0 (sv) * | 2000-10-20 | 2000-10-20 | Astrazeneca Ab | Pharmaceutically useful compounds |
| US6573264B1 (en) | 2000-10-23 | 2003-06-03 | Cv Therapeutics, Inc. | Heteroaryl alkyl piperazine derivatives |
| MXPA04000565A (es) * | 2001-07-19 | 2005-06-17 | Cv Therapeutics Inc | Compuestos de piperazina sustituidos y su uso como inhibidores de oxidacion de acidos grasos. |
-
2003
- 2003-12-05 AT AT03812835T patent/ATE365737T1/de not_active IP Right Cessation
- 2003-12-05 WO PCT/US2003/038867 patent/WO2004052887A2/en not_active Ceased
- 2003-12-05 EP EP03812835A patent/EP1567525B1/de not_active Expired - Lifetime
- 2003-12-05 ES ES07008429T patent/ES2327873T3/es not_active Expired - Lifetime
- 2003-12-05 DE DE60328545T patent/DE60328545D1/de not_active Expired - Lifetime
- 2003-12-05 KR KR1020057010236A patent/KR20050084182A/ko not_active Ceased
- 2003-12-05 CA CA002508608A patent/CA2508608A1/en not_active Abandoned
- 2003-12-05 NZ NZ540548A patent/NZ540548A/en unknown
- 2003-12-05 DE DE60314662T patent/DE60314662T2/de not_active Expired - Lifetime
- 2003-12-05 JP JP2004559388A patent/JP2006510670A/ja active Pending
- 2003-12-05 ES ES03812835T patent/ES2287574T3/es not_active Expired - Lifetime
- 2003-12-05 AU AU2003300827A patent/AU2003300827B2/en not_active Ceased
- 2003-12-05 US US10/729,499 patent/US7125876B2/en not_active Expired - Fee Related
-
2006
- 2006-09-07 US US11/518,085 patent/US7407960B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| AU2003300827A1 (en) | 2004-06-30 |
| HK1111683A1 (en) | 2008-08-15 |
| DE60314662D1 (de) | 2007-08-09 |
| DE60314662T2 (de) | 2008-03-13 |
| EP1567525A2 (de) | 2005-08-31 |
| US20040152890A1 (en) | 2004-08-05 |
| HK1083492A1 (en) | 2006-07-07 |
| US7125876B2 (en) | 2006-10-24 |
| WO2004052887A3 (en) | 2004-07-15 |
| DE60328545D1 (de) | 2009-09-03 |
| CA2508608A1 (en) | 2004-06-24 |
| JP2006510670A (ja) | 2006-03-30 |
| EP1567525B1 (de) | 2007-06-27 |
| US7407960B2 (en) | 2008-08-05 |
| AU2003300827B2 (en) | 2009-08-13 |
| WO2004052887A2 (en) | 2004-06-24 |
| ATE365737T1 (de) | 2007-07-15 |
| NZ540548A (en) | 2008-03-28 |
| KR20050084182A (ko) | 2005-08-26 |
| ES2287574T3 (es) | 2007-12-16 |
| US20070004751A1 (en) | 2007-01-04 |
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